The macula is the part of the retina which is responsible for sharp vision, due to the presence of a high density of cone photoreceptors. Macular oedema is a condition characterised by swelling of the macula due to leakage from small blood vessels. There is a breakdown of blood retinal bathers with changes in microvascular permeability, which leads to extracellular oedema, photoreceptor damage and loss of vision.
Macular oedema is caused by a wide range of retinal diseases which include:
1) Wet age-related macular degeneration,
2) Diabetic maculopathy,
3) Retinal vascular occlusions (branch or central),
4) Epiretinal membranes, and
5) Inflammation within the eye such as after recent eye surgery.
Vision loss associated with the above conditions is due to macular oedema, and the main strategy to reduce visual loss in patients having the above conditions has been the treatment of macular oedema. Age-related macular degeneration is the leading cause of visual impairment and blindness in persons over the age of 65 in the world. The condition, which occurs in dry and wet forms, usually affects older adults resulting in a loss of vision in the centre of the visual field, due to retina damage. In dry age-related macular degeneration, drusen (cellular debris) builds up between the retina and choroid. In the more severe wet form, blood vessels may grow up from the choroid behind the retina, leading to blood and protein leakage beneath the macula and consequences such as vision loss and detached retinas.
Diabetic retinopathy (also referred to as diabetic maculopathy) is the most common cause of blindness among adults of working age, and involves swelling of the central part of the retina or the macula. Diabetic retinopathy is caused by changes in the blood vessels of the retina. For some people with the condition, blood vessels may swell and leak fluid and/or abnormal new blood vessels may grow on the surface of the retina. Diabetic retinopathy has been classified as having four stages:
i) Mild non-proliferative diabetic retinopathy (in which microaneurysms occur—small areas of balloon-like swelling in the blood vessels of the retina);
ii) Moderative non-proliferative diabetic retinopathy (in which some blood vessels which nourish the retina are blocked);
iii) Severe non-proliferative diabetic retinopathy (in which many more blood vessels are blocked depriving areas of the retina of blood supply); and
iv) Proliferative diabetic retinopathy (in which the growth of new blood vessels takes place. The blood vessels can leak blood resulting in severe vision loss and/or blindness).
Diabetic retinopathy is responsible for 12,000 to 24,000 new cases of blindness each year in the USA. Macular oedema affects 14% of patients with diabetes.
Retinal vascular occlusion diseases (e.g. by thrombus formation blocking blood supply in arteries to the retina) are the second most common cause of visual loss due to retinal vascular disease. They affect around 1.1 million people in the USA alone, thus representing a serious public health problem.
Epiretinal membrane is a condition affecting the macula in which a layer of tissue forms across the macula which contracts to create tension, and can lead to macula oedema.
The main strategy to reduce visual loss in these patients has been by treatment with VEGF inhibitors. VEGF inhibitors have revolutionised the way in which patients with wet age-related macular degeneration are treated in the last 5 years. Intravitreal injections of VEGF inhibitors (e.g. Avastin® (bevacizumab), Lucentis® (ranibizumab)) have been used to treat macular oedema, and give visual outcomes superior to previous treatments. However, although positive effects are observed whilst patients are on treatment, oedema tends to return when treatment is stopped. Frequent monthly intravitreal injections lead to better outcomes for patients. However, side effects such as endophthalmitis, retinal tears leading to retinal detachments, vitreous haemorrhages and cataracts are observed with repeated injections.
Intravitreal injections of steroids, such as Kenalog® (triamcinolone) have also been used to treat macular oedema. However treatment effects are usually temporary and therapy needs to be repeated. Intravitreal steroids can also cause side effects such as increased intraocular pressure, cataracts, retinal detachment, vitreous haemorrhages and endophthalmitis. In diabetic retinopathy, focal or grid laser photocoagulation is the standard of care for the past 25 years. From the ETDRS study it is known that performing focal or grid laser reduces the risk of moderate vision loss as compared with no treatment. However, only 17% of patients gained vision. This means that nine patients have to be treated, for one to have improved vision.
Conditions causing damage to retinal photoreceptors and/or retinal pigment epithelial cells include inherited diseases such as retinitis pigmentosa and Stargardt's disease, damage caused by exposure to extreme light, damage associated with surgery (e.g. cataract surgery), damage associated with exposure to chemical toxins (e.g. quinines, such as chloroquine) and other conditions such as macular dystrophy and macular degeneration (e.g. dry age-related macular degeneration).
Dry eyes (also known as dry eye disease, dry eye syndrome) is a condition in which the eyes do not produce enough tears, and can lead to the eyes becoming inflamed or swollen. The condition has been defined as being a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear flim instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface (The Definition and Classification of Dry Eye Disease, Guidelines from the 2007 International Dry Eye Workshop, Lemp and Foulks). Dry eyes can cause irritation, reduced visual acuity, superficial punctuate keratitis and poor tear break-up time. The disease has been classified based on severity into 4 levels, ranging from levels 1 and 2 (mild), to levels 3 (moderate) and 4 (severe) (The Definition and Classification of Dry Eye Disease, supra).
Known therapies for dry eyes include treatment with artificial tear drops, steroidal and non-steroidal eye drops, cyclosporine eye drops, use of punctal plugs, use of specialized eyewear, and/or surgery. However, there are still patients with dry eyes who remain very symptomatic despite the use of such treatments.
The use of compositions containing omega-3 fatty acids in treating and/or preventing eye conditions has been investigated. For example, WO2010/118761 (Eolas Science Limited) discloses processes for preparing certain compositions rich in the omega-3 fatty acid docosahexaenoic acid (DHA) and which contain only low amounts of phytanic acid. WO2010/118761 also discloses the use of those compositions for treating certain eye conditions. US 2009/0226547 (Gilbard & Seddon) discloses a nutritional supplement for eye health comprising EPA and DHA together with anti-oxidant and anti-angiogenic components.
However, there remains a need for effective alternative therapies for treating conditions such as macular oedema, conditions causing damage to retinal photoreceptors and/or retinal pigment epithelial cells, and dry eyes.